Understanding antidepressant discontinuation syndrome (ADS) through preclinical experimental models

Konstantin N. Zabegalov, Tatiana O. Kolesnikova, Sergey L. Khatsko, Andrey D. Volgin, Oleg A. Yakovlev, Tamara G. Amstislavskaya, Polina A. Alekseeva, Darya A. Meshalkina, Ashton J. Friend, Wandong Bao, Konstantin A. Demin, Raul R. Gainetdinov, Allan V. Kalueff

    Research output: Contribution to journalReview articlepeer-review

    7 Citations (Scopus)


    Antidepressant drugs are currently one of the most prescribed medications. In addition to treatment resistance and side effects of antidepressants, their clinical use is further complicated by antidepressant discontinuation syndrome (ADS). ADS is a common problem in patients following the interruption, dose reduction, or discontinuation of antidepressant drugs. Clinically, ADS resembles a classical drug withdrawal syndrome, albeit differing from it because antidepressants generally do not induce addiction. The growing clinical importance and prevalence of ADS necessitate novel experimental (animal) models of this disorder. Currently available preclinical models of ADS are mainly rodent-based, and study mostly serotonergic antidepressants and their combinations. Here, we systematically assess clinical ADS symptoms and discuss current trends and challenges in the field of experimental (animal) models of ADS. We also outline basic mechanisms underlying ADS pathobiology, evaluate its genetic, pharmacological and environmental determinants, and emphasize how using animal models may help generate important translational insights into human ADS condition, its prevention and therapy.

    Original languageEnglish
    Pages (from-to)129-140
    Number of pages12
    JournalEuropean Journal of Pharmacology
    Publication statusPublished - 15 Jun 2018


    • Animal models
    • Antidepressants
    • Depression
    • Discontinuation syndrome
    • Side effects
    • Antidepressive Agents/adverse effects
    • Animals
    • Humans
    • Substance Withdrawal Syndrome/etiology
    • Disease Models, Animal

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